The Enteric Nervous System in Chagasic and Idiopathic Megacolon

Abstract

Chagas disease frequently causes megacolon. We investigated the enteric nervous systems in patients with chagasic megacolon compared to idiopathic megacolon and controls. Surgical specimens were obtained from 12 patients with chagasic megacolon (1 woman, 11 men, age range 41 to 72 y) and 9 patients with idiopathic megacolon (3 women, 6 men, age range 39 to 68 y), undergoing surgery for intractable constipation. A control group of 10 patients (9 women, 1 man, age range 43 to 75 y) undergoing left hemicolectomy for nonobstructing colorectal cancer was also studied. Colonic sections were investigated by conventional and immunohistochemical methods, also taking into consideration the presence of lymphocytes. Compared to controls, the 2 megacolon groups showed a decrease of enteric neurons (not due to increased apoptosis) and of enteric glial cells (all more important in chagasic patients). The interstitial cells of Cajal subtypes were decreased but not absent in megacolons, although an increase of the intramuscular subtype was found, suggesting a possible compensative mechanism. An increased amount of fibrosis was found in the smooth muscle and the myenteric plexus of chagasic patients compared to the idiopathic megacolon and the control group. A mild lymphocytic infiltration of the enteric plexuses (more evident in Chagas disease) was also found in megacolons but not in controls. Patients with chagasic megacolon display important abnormalities of several components of the enteric nervous system. Similar alterations, although of lesser severity, may be found in patients with idiopathic megacolon.

The pathophysiology of chagasic megacolon: beyond ICC…

“…The strength of this study relies in the fact that the authors took into consideration patients without overt megacolon and the cell count was carried out in complete intestinal rings that allowed them to correct the neuron and ICC dispersion due to intestinal dilation and muscular hypertrophy of the megacolon. The findings of ICC decrease were consistent with previous studies in chagasic patients with megacolon [2][3][4]. However, in our study, we found an increase of one of the three colonic populations of ICC, the intramuscular, and we disagree with the interpretation of Adad et al that this increase might have been due to an inclusion of mast cells in the count, since these were specifically excluded, as specified in the paper [4]; on the other hand, in our experience the distribution of ICC within the human colon is fairly homogeneous (Bassotti and Villanacci, unpublished observations).…”

“…This fact, in addition to the significant decrease of enteric glial cells we also found in patients with megacolon and other conditions characterized by constipation [4,5] strongly suggests that the development of megacolon requires enteric denervation and that an ICC decrease is an ancillary finding to neurogliopathic abnormalities.…”

“…However, in our study, we found an increase of one of the three colonic populations of ICC, the intramuscular, and we disagree with the interpretation of Adad et al that this increase might have been due to an inclusion of mast cells in the count, since these were specifically excluded, as specified in the paper [4]; on the other hand, in our experience the distribution of ICC within the human colon is fairly homogeneous (Bassotti and Villanacci, unpublished observations). More importantly, in their paper Adad et al did not distinguish between the three well established populations of colonic ICC, i.e., ICC submucous (along the submucosal surface of the circular muscle bundle), ICC myenteric (within the intermuscular space between circular and longitudinal muscle layers, myenteric region, which displays the highest yield of ICC in normal tissue), and ICC intramuscular (within the muscle fibers of the circular and longitudinal muscle layers) [4]. This fact might have led to a decreased cell count due to a different methodologic approach.…”

The development of chagasic megacolon requires severe denervation and the reduction in interstitial cells of Cajal number might be a contributing factor

“…Hypotheses were raised trying to explain the discrepancy with the results published by Iantorno et al [5]. Bassotti and Villanacci [1] claim that the hypotheses we proposed (inclusion of mast cells and heterogeneous distribution of ICC in different regions of the colon) are unfounded.…”

Rapid induction of mucosal healing by intensive granulocyte and monocyte adsorptive aphaeresis in active ulcerative colitis patients without concomitant corticosteroid therapy

“…Mast cells have been deeply investigated in systemic mastocytosis, 2 and irritable bowel syndrome patients, 3,4 but only a few studies have been published regarding chronic constipation, and most of them are related to Chagas' and Hirschsprung's disease. 5 The pathogenesis of gastrointestinal symptoms in mastocytosis remains unclear; abdominal pain, diarrhoea, peptic disease and malabsorption are the main clinical manifestations in systemic mastocytosis. 2 Recent investigations have shown that histamine induces the neural hypertrophy and increases mast cells in the gastrointestinal tract.…”